Glymphatic dysfunction in drug-resistant epilepsy and its association with vagus nerve stimulation outcomes: a...

The glymphatic system (GS) is critical for interstitial fluid clearance and has been implicated in various neurological disorders. However, its role in drug-resistant epilepsy (DRE) and response to vagus nerve stimulation (VNS) remains unclear.

This study aimed to assess GS function in patients with DRE using diffusion tensor image analysis along the perivascular space (DTI-ALPS) and to explore its association with VNS outcomes.

Data from patients with DRE who underwent VNS were retrospectively analyzed at a single center.

Forty patients with DRE and 30 healthy controls were enrolled. ALPS indices were calculated for the left (ALPS-L), right (ALPS-R), and bilateral (ALPS-B) hemispheres. The clinical outcomes after VNS were classified using McHugh outcome classification. Statistical comparisons and logistic regression were used to examine group differences and the predictive value of ALPS indices.

Compared to controls, patients with DRE exhibited significantly reduced ALPS-L (p < 0.001) and ALPS-B (p = 0.005) indices. Among patients with DRE, responders to VNS had significantly higher ALPS-R (p = 0.021) and ALPS-B (p = 0.027) indices than nonresponders. ALPS-L exhibited a positive trend (p = 0.073). In logistic regression analyses, ALPS-R and ALPS-B were significantly associated with favorable VNS outcomes in univariate and multivariate models. After adjusting for age, sex, and disease duration, ALPS-L (p = 0.028, odds ratio (OR) = 2.739), ALPS-R (p = 0.020, OR = 2.802), and ALPS-B (p = 0.020, OR = 3.241) all emerged as independent predictors of VNS response.

Glymphatic dysfunction is present in DRE and may influence responsiveness to VNS. Higher ALPS indices predicted better treatment outcomes, supporting ALPS potential as a noninvasive imaging biomarker for presurgical stratification in epilepsy.